rs16870603

Variant names:

• chr5-41002656-G-A
• rs16870603
• NM_173489.5:c.4194+1690C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173489.5(MROH2B):​c.4194+1690C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,098 control chromosomes in the GnomAD database, including 2,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2118 hom., cov: 32)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801
• Publications: 4 publications found

Genes affected

MROH2B (HGNC:26857): (maestro heat like repeat family member 2B) Predicted to be involved in protein kinase A signaling. Predicted to be located in acrosomal vesicle and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

C7 (HGNC:1346): (complement C7) This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

C7 Gene-Disease associations (from GenCC):

• complement component 7 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	NM_173489.5	MANE Select	c.4194+1690C>T		intron	N/A	NP_775760.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.4194+1690C>T		intron	N/A	ENSP00000382476.4	Q7Z745-1
	MROH2B	ENST00000506092.6	TSL:2	c.2859+1690C>T		intron	N/A	ENSP00000441504.1	F5GZ06
	MROH2B	ENST00000503890.5	TSL:2	n.3336+1690C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23585 AN: 151980 Hom.: 2115 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23599 AN: 152098 Hom.: 2118 Cov.: 32 AF XY: 0.157 AC XY: 11693 AN XY: 74350

African (AFR) AF: 0.0820 AC: 3406 AN: 41516

American (AMR) AF: 0.118 AC: 1803 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1362 AN: 5156

South Asian (SAS) AF: 0.213 AC: 1028 AN: 4826

European-Finnish (FIN) AF: 0.216 AC: 2281 AN: 10550

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12343 AN: 67974

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.172 Hom.: 4075

Bravo AF: 0.145

Asia WGS AF: 0.273 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16870603; hg19: chr5-41002758;